Since the discovery of norfloxacin, synthetic quinolone antibacterial drugs have been improved in their antibacterial activity and pharmacokinetics, and many compounds have been employed in the clinical field as chemotherapeutic agents which are effective for almost all systemic infectious diseases.
However, in recent years, bacteria exhibiting low sensitivity to synthetic quinolone antibacterial drugs have become increasingly common in the clinical field. For example, there has been an increase in Gram-positive bacteria which exhibit resistance to drugs other than synthetic quinolone antibacterial drugs and exhibit low sensitivity to synthetic quinolone antibacterial drugs, including β-lactam-insensitive Gram-positive cocci such as Staphylococcus aureus (MRSA) and Streptococcus neumoniae (PRSP), and aminoglycoside-antibacterial-drug-insensitive Enterococcus (VRE). Therefore, particularly in the clinical field, demand has arisen for a drug exhibiting higher efficacy on Gram-positive cocci.
As has been shown, when administered in combination with nonsteroidal anti-inflammatory drugs (NSAIDs), some synthetic quinolone antibacterial drugs cause side effects, including convulsion, central actions (e.g., mild central nervous disorders such as stagger, headache, and insomnia, and severe side effects such as convulsion), phototoxicity (photosensitivity), hepatotoxicity, cardiotoxicity (fatal-arrhythmia-inducing abnormality which is observed as abnormal electrocardiogram), and abnormal blood glucose level. Therefore, demand has arisen for development of a synthetic quinolone antibacterial drug exhibiting higher safety (see, for example, Non-Patent Document 1).
As has been known, the antibacterial activity, pharmacokinetics, and safety of a synthetic quinolone antibacterial drug are greatly affected by the structure of a substituent which is present at position 7 (or a position corresponding thereto) of the quinolone skeleton. Quinolone derivatives in which the quinolone skeleton is substituted, at position 7, with a 3-amino-4-methylpyrrolidin-1-yl group have been known to exhibit potent antibacterial activity to Gram-negative and Gram-positive bacteria (see, for example, Non-Patent Documents 2 and 3).
However, most of the aforementioned 3-amino-4-methylpyrrolidin-1-yl-group-substituted quinolone derivatives exhibit high incidence of chromosomal aberration, potent cytotoxicity, potent mouse or rat bone marrow micronucleus induction, and low selective toxicity, as compared with the case of quinolone derivatives having, as a substituent, a substituted or non-substituted piperazinyl group. Therefore, such a 3-amino-4-methylpyrrolidin-1-yl-group-substituted quinolone derivative acts on bacteria and as well on eukaryotic cells (see Non-Patent Document 3), and thus is difficult to employ as a drug or a veterinary drug. In practice, such a quinolone derivative has not yet been employed clinically.
Known quinolone derivatives substituted at position 7 with a 3-amino-4-alkylpyrrolidin-1-yl-group, which are related to the compound of the present invention, are described below (see Patent Documents 1 and 2).

The substituents of a compound of this formula are defined in Patent Document 1, etc. Although the substituents may be denoted by symbols that are common to those as used herein, the definitions provided in the prior art should be considered as irrelevant to those of the present invention. Specifically disclosed is merely a compound in which the substituent at position 4 of a pyrrolidinyl group (corresponding to the group R2) is a methyl group.
Patent Documents 3 and 4 disclose a compound having the following structure; specifically, merely a compound in which the substituent at position 4 of a pyrrolidinyl group is a methyl group (the substituents of this compound are defined in Patent Document 3, etc., and thus, even when the substituents are represented by the same symbols as used herein, they are irrelevant to those as defined herein).

Patent Documents 3 and 4 also disclose a compound having the following pyridobenzoxazine skeleton. The compound, in which the substituent at position 7 is a cis-3-amino-4-methylpyrrolidin-1-yl group, is a diastereomeric mixture.

Patent Document 5 discloses a compound having the following structure, in which the substituent at position 4 of a pyrrolidinyl group (corresponding to the group R2) is a methyl group, and the substituent at position 1 of the quinolone skeleton (corresponding to the group R1) is a 2-fluorocyclopropyl group (the substituents of the compound disclosed in Patent Document 5 are defined in Patent Document 5, and thus, even when the substituents are represented by the same symbols as used herein, they are irrelevant to those as defined herein). According to this patent document, the 1-position substituent is preferably a non-substituted cyclopropyl group.

Patent Document 6 does not disclose a compound in which the 1-position substituent is a halogenocyclopropyl group.
Patent Document 7 discloses a compound in which the substituent at position 4 of a pyrrolidinyl group is an ethyl group, but does not describe specific examples of the compound. In addition, the substituent at position 1 of the quinolone skeleton is limited to a non-substituted cyclopropyl group.
Patent Documents 8 and 9 disclose a compound in which the substituent at position 4 of a pyrrolidinyl group (corresponding to the group R1) is an ethyl group (the substituents of the compound disclosed in Patent Documents 8 and 9 are defined in Patent Document 8, etc., and thus, even when the substituents are represented by the same symbols as used herein, they are irrelevant to those as defined herein). However, the substituent at position 1 of the quinolone skeleton is a non-substituted cyclopropyl group.

Patent Documents 10 and 11 disclose a compound having the following structure.
    Patent Document 1: Specification of JP Patent No. 2917010    Patent Document 2: Specification of U.S. Pat. No. 5,587,386    Patent Document 3: Specification of European Patent No. 208210    Patent Document 4: Specification of U.S. Pat. No. 4,753,953    Patent Document 5: JP-A-SHO63-264461    Patent Document 6: U.S. Pat. No. 4,855,292    Patent Document 7: JP-A-SHO64-83068    Patent Document 8: WO 96/22988 pamphlet    Patent Document 9: JP-A-HEI8-259561Patent Document 10: Specification of European Patent No. 242789    Patent Document 11: Specification of U.S. Pat. No. 4,886,810    Non-Patent Document 1: Clinical Application of New Quinolone Agent, edited by Hiroyuki Kobayashi, Iyaku Journal Co., Ltd. (2001)    Non-Patent Document 2: International Journal of Antimicrobial Agents, Vol. 16, p. 5 (2000)    Non-Patent Document 3: Journal of Antimicrobial Chemotherapy, Vol. 33, p. 685 (1994)